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T cell exhaustion is associated with antigen abundance and promotes transplant acceptance.

Authors
  • Zou, Dawei1, 2
  • Dai, Yulin3
  • Zhang, Xiaolong1
  • Wang, Guohua1
  • Xiao, Xiang1
  • Jia, Peilin3
  • Li, Xian C1, 4
  • Guo, Zhiyong2
  • Chen, Wenhao1, 4
  • 1 Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute and Institute for Academic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
  • 2 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. , (China)
  • 3 Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • 4 Department of Surgery, Weill Cornell Medicine, Cornell University, New York, New York, USA.
Type
Published Article
Journal
American Journal of Transplantation
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2020
Volume
20
Issue
9
Pages
2540–2550
Identifiers
DOI: 10.1111/ajt.15870
PMID: 32185888
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Exhaustion of T cells limits their ability to clear chronic infections or eradicate tumors. Here, in the context of transplant, we investigated whether T cell exhaustion occurs and has a role in determining transplant outcome. A peptide/MHC tetramer-based approach was used to track exhausted CD8+ T cells in a male-to-female skin transplant model. Transplant of large whole-tail skins, but not small tail skins (0.8 cm × 0.8 cm), led to exhaustion of anti-male tetramer+ CD8+ T cells and subsequently the acceptance of skin grafts. To study CD4+ T cell exhaustion, we used the TCR-transgenic B6 TEa cells that recognize a major transplant antigen I-Eα from Balb/c mice. TEa cells were adoptively transferred either into B6 recipients that received Balb/c donor skins or into CB6F1 mice that contained an excessive amount of I-Eα antigen. Adoptively transferred TEa cells in skin-graft recipients were not exhausted. By contrast, virtually all adoptively transferred TEa cells were exhausted in CB6F1 mice. Those exhausted TEa cells lost ability to reject Balb/c skins upon further transfer into lymphopenic B6.Rag1-/- mice. Hence, T cell exhaustion develops in the presence of abundant antigen and promotes transplant acceptance. These findings are essential for better understanding the nature of transplant tolerance. © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.

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